tbuckley/cabot-search huggingface dataset:
Stimulus‐Detonated Biomimetic “Nanobomb” with Controlled Release of HSP90 Inhibitor to Disrupt Mitochondrial Function for Synergistic Gas and Photothermal Therapy
Authors: Geng Yang, Ting Song, Hanxi Zhang, Mengyue Li, Xiaodan Wei, Wanyi Zhou, Chunhui Wu, Yiyao Liu, Hong Yang
Journal: Advanced Healthcare Materials (2023)

Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H2 O2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn2+ enables T1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.
PI16+ reticular cells in human palatine tonsils govern T cell activity in distinct subepithelial niches
Authors: Angelina De Martin, Yves Stanossek, Mechthild Lütge, Nadine Cadosch, Lucas Onder, Hung-Wei Cheng, Joshua D. Brandstadter, Ivan Maillard, Sandro J. Stoeckli, Natalia B. Pikor, Burkhard Ludewig
Journal: Nature Immunology (2023)

Abstract Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role in steering innate and adaptive immunity, the age- and inflammation-associated changes in the molecular identity and functional properties of human FRCs have remained largely unknown. Here, we show that human tonsillar FRCs undergo dynamic reprogramming during life and respond vigorously to inflammatory perturbation in comparison to other stromal cell types. The peptidase inhibitor 16 (PI16)-expressing reticular cell (PI16 + RC) subset of adult tonsils exhibited the strongest inflammation-associated structural remodeling. Interactome analysis combined with ex vivo and in vitro validation revealed that T cell activity within subepithelial niches is controlled by distinct molecular pathways during PI16 + RC–lymphocyte interaction. In sum, the topological and molecular definition of the human tonsillar stromal cell landscape reveals PI16 + RCs as a specialized FRC niche at the core of mucosal immune responses in the oropharynx.
Conserved stromal–immune cell circuits secure B cell homeostasis and function
Authors: Mechthild Lütge, Angelina De Martin, Cristina Gil-Cruz, Christian Perez-Shibayama, Yves Stanossek, Lucas Onder, Hung-Wei Cheng, Lisa Kurz, Nadine Cadosch, Charlotte Soneson, Mark D. Robinson, Sandro J. Stoeckli, Burkhard Ludewig, Natalia B. Pikor
Journal: Nature Immunology (2023)

Abstract B cell zone reticular cells (BRCs) form stable microenvironments that direct efficient humoral immunity with B cell priming and memory maintenance being orchestrated across lymphoid organs. However, a comprehensive understanding of systemic humoral immunity is hampered by the lack of knowledge of global BRC sustenance, function and major pathways controlling BRC–immune cell interactions. Here we dissected the BRC landscape and immune cell interactome in human and murine lymphoid organs. In addition to the major BRC subsets underpinning the follicle, including follicular dendritic cells, PI16 + RCs were present across organs and species. As well as BRC-produced niche factors, immune cell-driven BRC differentiation and activation programs governed the convergence of shared BRC subsets, overwriting tissue-specific gene signatures. Our data reveal that a canonical set of immune cell-provided cues enforce bidirectional signaling programs that sustain functional BRC niches across lymphoid organs and species, thereby securing efficient humoral immunity.
An integrated tumor, immune and microbiome atlas of colon cancer
Authors: Jessica Roelands, Peter J. K. Kuppen, Eiman I. Ahmed, Raghvendra Mall, Tariq Masoodi, Parul Singh, Gianni Monaco, Christophe Raynaud, Noel F.C.C. de Miranda, Luigi Ferraro, Tatiana C. Carneiro-Lobo, Najeeb Syed, Arun Rawat, Amany Awad, Julie Decock, William Mifsud, Lance D. Miller, Shimaa Sherif, Mahmoud G. Mohamed, Darawan Rinchai, Marc Van den Eynde, Rosalyn W. Sayaman, Elad Ziv, Francois Bertucci, Mahir Abdulla Petkar, Stephan Lorenz, Lisa Sara Mathew, Kun Wang, Selvasankar Murugesan, Damien Chaussabel, Alexander L. Vahrmeijer, Ena Wang, Anna Ceccarelli, Khalid A. Fakhro, Gabriele Zoppoli, Alberto Ballestrero, Rob A.E.M. Tollenaar, Francesco M. Marincola, Jérôme Galon, Souhaila Al Khodor, Michele Ceccarelli, Wouter Hendrickx, Davide Bedognetti
Journal: Nature Medicine (2023)

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.
Fair pathways to net-zero healthcare
Authors: Anand Bhopal, Ole F. Norheim
Journal: Nature Medicine (2023)

Over the past decade, it has become clear that the health sector is not only at risk from climate change but also a major polluter of greenhouse gases. In November 2021, the World Health Organization and partners launched the COP26 Health Programme for sustainable, climate-resilient and low-carbon health systems, and have since established the Alliance for Transformative Action on Climate and Health to support its implementation. Given the wide variation in health financing, carbon emissions and unmet health needs across the world, fair sharing of the remaining carbon budget and health gains will be critical. In this Perspective, we explore the challenges and opportunities of healthcare decarbonization, outlining the principles of fair pathways to net-zero healthcare that are attentive to health and socioeconomic inequalities within and between countries. The health sector must play its part in decarbonization efforts; this Perspective outlines the principles of fair pathways to net-zero healthcare that are attentive to health and socioeconomic inequalities.
Pervasive SUMOylation of heterochromatin and piRNA pathway proteins
Authors: Maria Ninova, Hannah Holmes, Brett Lomenick, Katalin Fejes Tóth, Alexei A. Aravin
Journal: Cell Genomics (2023)

Genome regulation involves complex protein interactions that are often mediated through post-translational modifications (PTMs). SUMOylation-modification by the small ubiquitin-like modifier (SUMO)-has been implicated in numerous essential processes in eukaryotes. In
Social participation and risk of developing dementia
Authors: Andrew Sommerlad, Mika Kivimäki, Eric B. Larson, Susanne Röhr, Kokoro Shirai, Archana Singh-Manoux, Gill Livingston
Journal: Nature Aging (2023)

The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect dementia risk by increasing cognitive reserve, and through brain maintenance by reducing stress and improving cerebrovascular health. It may therefore have important implications for individual behavior and public health policy aimed at reducing dementia burden. Observational study evidence indicates that greater social participation in midlife and late life is associated with 30–50% lower subsequent dementia risk, although some of this may not be causal. Social participation interventions have led to improved cognition but, partly due to short follow-up and small numbers of participants, no reduction in risk of dementia. We summarize the evidence linking social participation with dementia, discuss potential mechanisms by which social participation is likely to reduce and mitigate the impact of neuropathology in the brain, and consider the implications for future clinical and policy dementia prevention interventions. This Review provides evidence-based update on the association between social interaction and risk of dementia. The authors propose a policy framework to promote social interaction as a preventative strategy against dementia.
Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development
Authors: Dylan E. Hughes, Keiko Kunitoki, Safia Elyounssi, Mannan Luo, Oren M. Bazer, Casey E. Hopkinson, Kevin F. Dowling, Alysa E. Doyle, Erin C. Dunn, Hamdi Eryilmaz, Jodi M. Gilman, Daphne J. Holt, Eve M. Valera, Jordan W. Smoller, Charlotte A. M. Cecil, Henning Tiemeier, Phil H. Lee, Joshua L. Roffman
Journal: Nature Neuroscience (2023)
Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)
Authors: Yunpeng Yang, Jianji Pan, Hui Wang, Yuanyuan Zhao, Shenhong Qu, Nianyong Chen, Xiaozhong Chen, Yan Sun, Xiaohui He, Chaosu Hu, Lizhu Lin, Qitao Yu, Siyang Wang, Guihua Wang, Feng Lei, Jiyu Wen, Kunyu Yang, Zhixiong Lin, Ye Guo, Shaoqing Chen, Xiaoming Huang, Yanjie Wu, Liang Liang, Chenqi Chen, Fan Bai, Xiaopeng Ma, Yun Zhang, Shiangjiin Leaw, Li Zhang, Wenfeng Fang
Journal: Cancer Cell (2023)

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo-chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumab-chemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot" tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment. VIDEO ABSTRACT.
Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma
Authors: Alexandra Lahtinen, Kari Lavikka, Anni Virtanen, Yilin Li, Sanaz Jamalzadeh, Aikaterini Skorda, Anna Røssberg Lauridsen, Kaiyang Zhang, Giovanni Marchi, Veli-Matti Isoviita, Valeria Ariotta, Oskari Lehtonen, Taru A. Muranen, Kaisa Huhtinen, Olli Carpén, Sakari Hietanen, Wojciech Senkowski, Tuula Kallunki, Antti Häkkinen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Journal: Cancer Cell (2023)

Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features in genomics, pathways, and morphological phenotypes, and significant association with treatment response. Nested pathway analysis suggests two evolutionary trajectories between the states. Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts.
The CDC Domestic Mpox Response — United States, 2022–2023
Authors: Jennifer H. McQuiston, Christopher R. Braden, Michael D. Bowen, Andrea M. McCollum, Robert McDonald, Neal Carnes, Rosalind J. Carter, Athalia Christie, Jeffrey B. Doty, Sascha Ellington, S. Nicole Fehrenbach, Adi V. Gundlapalli, Christina L. Hutson, Rachel E. Kachur, Aaron Maitland, Christine M. Pearson, Joseph Prejean, Laura A. S. Quilter, Agam K. Rao, Yon Yu, Jonathan Mermin
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services.† A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).
Detection of trait-associated structural variations using short-read sequencing
Authors: Shunichi Kosugi, Yoichiro Kamatani, Katsutoshi Harada, Kohei Tomizuka, Yukihide Momozawa, Takayuki Morisaki, Chikashi Terao
Journal: Cell Genomics (2023)

Genomic structural variation (SV) affects genetic and phenotypic characteristics in diverse organisms, but the lack of reliable methods to detect SV has hindered genetic analysis. We developed a computational algorithm (MOPline) that includes missing call recovery combined with high-confidence SV call selection and genotyping using short-read whole-genome sequencing (WGS) data. Using 3,672 high-coverage WGS datasets, MOPline stably detected ∼16,000 SVs per individual, which is over ∼1.7-3.3-fold higher than previous large-scale projects while exhibiting a comparable level of statistical quality metrics. We imputed SVs from 181,622 Japanese individuals for 42 diseases and 60 quantitative traits. A genome-wide association study with the imputed SVs revealed 41 top-ranked or nearly top-ranked genome-wide significant SVs, including 8 exonic SVs with 5 novel associations and enriched mobile element insertions. This study demonstrates that short-read WGS data can be used to identify rare and common SVs associated with a variety of traits.
Prevalence of Disability by Occupation Group — United States, 2016–2020
Authors: Taylor M. Shockey, Kelsie Fox, Guixiang Zhao, NaTasha Hollis
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In 2020, approximately 21.5 million employed U.S. adults aged 18-64 years had some form of disability. Although 75.8% of noninstitutionalized persons without disability aged 18-64 were employed, only 38.4% of their counterparts with disability were employed (1). Persons with disability have job preferences similar to persons without disability but might encounter barriers (e.g., lower average training or education levels, discrimination, or limited transportation options) that affect the types of jobs they hold (2,3). CDC analyzed 2016-2020 Behavioral Risk Factor Surveillance System (BRFSS) data from 35 states and Guam to estimate disability prevalences, by type and occupation group, among currently employed U.S. adults aged 18-64 years. The highest adjusted disability prevalences were among workers in three of the 22 major occupation groups: food preparation and serving-related (19.9%); personal care and service (19.4%); and arts, design, entertainment, sports, and media (17.7%). Occupation groups with the lowest adjusted disability prevalences were business and financial operations (11.3%), health care practitioners and technicians (11.1%), and architecture and engineering (11.0%). The distributions of persons with and without disability differ across occupations. Workplace programs that address the training, education, and workplace needs of employees with disability might improve workers' ability to enter, thrive in, and advance in a wider range of occupations.
Abstracts
Authors: Masahiro Miyake, Shin-Ya Nakao, Kazuya Morino, Shota Yasukura, Yuki Mori, Kenji Ishihara, Yuki Muraoka, Manabu Miyata, Hiroshi Tamura, Taiji Sakamoto, Akitaka Tsujikawa
Journal: Ophthalmology (2023)
Organoids: The current status and biomedical applications
Authors: Siqi Yang, Haijie Hu, Hengchung Kung, Ruiqi Zou, Yushi Dai, Yafei Hu, Tiantian Wang, Tianrun Lv, Jun Yu, Fuyu Li
Journal: MedComm (2023)

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self-organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long-term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large-scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.
Pre‐discharge and early post‐discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC
Authors: Marco Metra, Marianna Adamo, Daniela Tomasoni, Alexandre Mebazaa, Antoni Bayes‐Genis, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Johann Bauersachs, Yuri Belenkov, Michael Böhm, Tuvia Ben Gal, Javed Butler, Alain Cohen‐Solal, Gerasimos Filippatos, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, Ewa A. Jankowska, Mitja Lainscak, Yuri Lopatin, Lars H. Lund, Theresa McDonagh, Davor Milicic, Brenda Moura, Wilfried Mullens, Massimo Piepoli, Marija Polovina, Piotr Ponikowski, Amina Rakisheva, Arsen Ristic, Gianluigi Savarese, Petar Seferovic, Rajan Sharma, Thomas Thum, Carlo G. Tocchetti, Sophie Van Linthout, Cristiana Vitale, Stephan Von Haehling, Maurizio Volterrani, Andrew J.S. Coats, Ovidiu Chioncel, Giuseppe Rosano
Journal: European Journal of Heart Failure (2023)
Searching for answers: prostate screening in a stretched NHS
Authors: Juliet Dobson
Journal: BMJ (2023)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Searching for answers: prostate screening in a stretched NHS Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Management of lateral epicondylitis (tennis elbow)
Authors: Marta Karbowiak, Thomas Holme, James Thambyrajah, Livio Di Mascio
Journal: BMJ (2023)

### What you need to know Lateral epicondylitis (also known as tennis elbow) is a common, often debilitating disorder frequently encountered in primary care across low and high resource settings.12 This article outlines current management strategies, including supportive measures, activity modification, and newer treatments that have emerged over the past 20 years, such as percutaneous needle fenestration and injection of autologous blood and platelet rich plasma. Lateral epicondylitis is a type of tendinosis, a degenerative process where repetitive stress causes fibroblast deposition with collagen disorganisation and vascular hyperplasia.3 Pain causes underuse of the affected arm and further weakening in the tendon structure, with possible sequelae of partial or complete rupture of the tendon.4 Cadaveric and electromyographic studies show that symptoms (namely, lateral elbow pain) are often related to excessive loading of the lateral extensor tendons, as well as repetitive wrist extension or supination movements.5 The condition commonly presents as a work related strain injury, and often affects tennis players6 (box 1). Box 1 ### Who gets it?RETURN TO TEXT